Enzymatic Route toward 6‐Methylated Baeocystin and Psilocybin
ChemBioChem – May 31, 2019
Source: OpenAlex
Summary
Revolutionary biochemistry now allows for the precise chemical synthesis of modified psilocybin, a key indole alkaloid. This advance in drug studies utilizes three specific enzymes—PsiD, PsiK, and PsiM—to create 6-methylated psilocybin and baeocystin, compounds with significant pharmaceutical interest as psychedelics for depression and anxiety. The process involves crucial methylation. An in silico model of the PsiM enzyme further clarifies its stereochemistry, revealing how its unique chemistry influences substrate preferences, advancing our understanding of alkaloids: synthesis and pharmacology.
Abstract
Abstract Psilocybin and its direct precursor baeocystin are indole alkaloids of psychotropic Psilocybe mushrooms. The pharmaceutical interest in psilocybin as a treatment option against depression and anxiety is currently being investigated in advanced clinical trials. Here, we report a biocatalytic route to synthesize 6‐methylated psilocybin and baeocystin from 4‐hydroxy‐6‐methyl‐ l ‐tryptophan, which was decarboxylated and phosphorylated by the Psilocybe cubensis biosynthesis enzymes PsiD and PsiK. N‐Methylation was catalyzed by PsiM. We further present an in silico structural model of PsiM that revealed a well‐conserved SAM‐binding core along with peripheral nonconserved elements that likely govern substrate preferences.